3-methoxy-N,N-dimethylpropionamide

Endpoint summary

Description of key information

LLNA (OECD 429): not sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 October 2006 - 24 October 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

24 April 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

other: CBA/Ca (CBA/CaBkl)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: B & K Universal Ltd, Hull, UK.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (eight to twelve weeks old)
- Weight at study initiation: 15 - 23 g
- Housing: Animals were individually housed in suspended solid-floor polypropylene cages.
- Diet: Free access to Certified Rat and Mouse Diet (Code 5LF2, supplied by BCM IPS Limited, London, UK)
- Water: Free access to mains tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (set conditions)
- Temperature (°C): 19 – 25
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0, 25, 50 and 100%

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:
As no toxicological information was available regarding the systemic toxicity/irritancy potential of the test material, a preliminary screening test was performed using one mouse. The mouse was treated by daily application of 25 µL of the undiluted test material, to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The mouse was observed twice daily on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Any signs of toxicity or excessive local irritation noted during this period were recorded. The bodyweight was recorded on Day 1 (prior to dosing) and on Day 6).

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: The test material will be regarded as a sensitiser if at least one concentration of the test material results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test material failing to produce a threefold or greater increase in 3HTdR incorporation will be classified as a "non-sensitiser".

ANIMAL ASSIGNMENT
Three groups of four animals were treated with one test substance concentration per group. One group of four animals was treated with vehicle.

TREATMENT PREPARATION AND ADMINISTRATION:
Test substance preparation: For the purpose of the study, the test material was used undiluted and freshly prepared in acetone/olive oil 4:1 by using a vortex mixer.
Rationale for vehicle: This vehicle was chosen as it produced the most suitable formulation at the required concentration.

Induction - Days 1, 2 and 3; Excision of nodes - Day 6; Tissue processing for radioacitivity - Day 6; Radioactivity measurements - Day 7; Performed according to test guidelines.

Observations:
Body weights: On Day 1 (pre-dose) and Day 6 (prior to necropsy).
Clinical signs: All animals were observed twice daily on Days 1, 2 and 3 and on a daily basis on Days 4, 5 and 6. Any signs of toxicity or signs of ill health during the test were recorded.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Not performed.

Positive control results:

The latest reliability check with Alpha-hexylcinnamicaldehyde indicates that the Local Lymph Node Assay as performed at SafePharm Laboratories is an appropriate model for testing for contact hypersensitivity (SI value of 4.03 and 9.13 at 10% and 25%, respectively).

Key result

Parameter:

SI

Value:

1.66

Test group / Remarks:

25%

Key result

Parameter:

SI

Value:

1.8

Test group / Remarks:

50%

Key result

Parameter:

SI

Value:

1.84

Test group / Remarks:

100%

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: The radioactive disintegrations per minute per lymph node for the substance concentrations 25, 50 and 100% were 1146, 1238 and 1264, respectively. And for the vehicle the radioactive disintegrations per minute per lymph node was 688.

Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION:
A stimulation index of less than 3 was recorded for the undiluted test material and the test material at concentrations of 50% and 25% v/v.

CLINICAL OBSERVATIONS:
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test.

BODY WEIGHTS:
Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.

Results Pre-screen test:

No signs of systemic toxicity were noted. Based on this information the undiluted test material and the test material at dose levels of 50% and 25% v/v were selected for the main test.

Interpretation of results:

other: Not sensitising.

Remarks:

According to Regulation (EC) No. 1272/2008.

Conclusions:

In an LLNA skin sensitisation study, performed according to OECD 429 test guideline and GLP principles, 3-methoxy-N,N-dimethylpropanamide was considered not to be a skin sensitiser, as the SI appeared not to be ≥ 3 when tested up to 100% v/v.

Executive summary:

An LLNA skin sensitisation study was performed according to OECD 429 test guideline and GLP principles. Based on the results of a pre-screen test, the test concentrations were selected at 25%, 50% and 100% v/v. There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test. Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.

Mean DPM/animal values for the experimental groups treated with test item concentrations 25, 50 and 100% were 1146, 1238 and 1264 DPM, respectively. The mean DPM/animal value for the vehicle control group was 688 DPM. The SI values calculated for the test item concentrations 25, 50 and 100% were 1.66, 1.80 and 1.84, respectively. As the SI appeared not to be ≥ 3 when tested up to 100% v/v, 3-methoxy-N,N-dimethylpropanamide was considered not to be a skin sensitiser according to Regulation (EC) No. 1272/2008.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

An LLNA skin sensitisation study was performed according to OECD 429 test guideline and GLP principles. Based on the results of a pre-screen test, the test concentrations were selected at 25%, 50% and 100% v/v.There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test. Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.

Mean DPM/animal values for the experimental groups treated with test item concentrations 25, 50 and 100% were 1146, 1238 and 1264 DPM, respectively. The mean DPM/animal value for the vehicle control group was 688 DPM. The SI values calculated for the test item concentrations 25, 50 and 100% were 1.66, 1.80 and 1.84, respectively. As the SI appeared not to be ≥ 3 when tested up to 100% v/v,3-methoxy-N,N-dimethylpropanamidewas considered not to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results, 3-methoxy-N,N-dimethylpropanamide does not have to be classified for skin sensitisation according to Regulation (EC) No. 1272/2008.